@article {3503, title = {In vivo detection of polyomaviruses JCV and SV40 in mesenchymal stem cells from human umbilical cords.}, journal = {Pediatr Blood Cancer}, volume = {61}, year = {2014}, month = {2014 Aug}, pages = {1347-9}, abstract = {

BACKGROUND: Multipotent stromal cells are present in the Wharton{\textquoteright}s jelly matrix (WJSC) of the umbilical cord and can be used as an allogeneic source of cells to treat immunological disorders. Recently it was demonstrated that adult bone marrow (BM)-derived mesenchimal stromal cells (MSC) are susceptible to infection with viruses showing potential oncogenic properties, such as the polyomavirus JC (JCV). The aim of this study was to investigate the presence of human polyomaviruses (JCV, BK Virus-BKV, SV40, and Merkel cell polyomavirus-MCPyV) in WJSC, and explore the risk of infection.

PROCEDURE: MSC samples from 35 umbilical cords were investigated by quantitative Real Time PCRs for the presence of DNA sequences of JCV, BKV, SV40, and MCPyV.

RESULTS: JCV DNA was detected in 1/35 (2.8\%) of MSC samples, while SV40 DNA was found in 3/35 (8.6\%) of the examined samples. None of the samples showed sequences of BKV and MCPyV.

CONCLUSIONS: The present study demonstrates the in vivo ability of polyomaviruses to infect WJSC. Since the therapeutic approach with the WJSC has high potentiality and a more intensive use can be easily hypothesized, the need to develop consensus guidelines to detect rare viral infections in MSC is pressing.

}, keywords = {DNA, Viral, Female, Fetal Blood, Humans, JC Virus, Male, Mesenchymal Stromal Cells, Polyomavirus Infections, Simian virus 40, Tumor Virus Infections}, issn = {1545-5017}, doi = {10.1002/pbc.24943}, author = {Comar, Manola and Delbue, Serena and Zanotta, Nunzia and Valencic, Erica and Piscianz, Elisa and Del Savio, Rossella and Tesser, Alessandra and Tommasini, Alberto and Ferrante, Pasquale} } @article {3485, title = {Inhibition of mesenchymal stromal cells by pre-activated lymphocytes and their culture media.}, journal = {Stem Cell Res Ther}, volume = {5}, year = {2014}, month = {2014}, pages = {3}, abstract = {

INTRODUCTION: Despite having a proven immunosuppressive potential in vitro, human mesenchymal stromal cells (MSCs) are reported to display variable efficacy in vivo and, in fact, their proven benefit in the clinical practice is still limited and controversial.

METHODS: The interplay between clinical grade MSCs and pre-activated donor lymphocytes or selected lymphocyte subsets was studied in vitro. The kinetics of MSC growth and viability was evaluated by adhesion-dependent changes of culture plate impedance and biochemically by a colorimetric assay. Activation of natural killer (NK) cells was assessed as well, using a flow cytometry assay.

RESULTS: A strong inhibition of MSC growth was rapidly induced by the addition of pre-activated lymphocytes but not of resting lymphocytes. Inhibition seems not to be attributable to a single cell population, as similar results can be obtained by depleting NK cells or by using either selected CD4+ or CD8+ lymphocytes. In addition, conditioned medium (CM) from activated lymphocytes was able to inhibit MSC growth in a dose-dependent manner. Furthermore, licensing with IFN-γ partially protected MSCs from pre-activated lymphocytes but not from their CM. These results suggest an inhibitory role of lymphocyte-activation-derived substances. However, the identification of a single molecule responsible for MSC inhibition remained elusive, even if preliminary experiments showed that ATP and, to a lesser extent, TNF-α might play a role.

CONCLUSIONS: These results suggest that survival of MSCs can be affected by soluble mediators released by activated lymphocytes. Thus it can be hypothesized that MSC immunosuppressive action in vivo could be impaired by ongoing immune activation through the release of inflammatory mediators.

}, keywords = {CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Proliferation, Cell Survival, Cells, Cultured, Coculture Techniques, Culture Media, Conditioned, Cytokines, Humans, Killer Cells, Natural, Lymphocyte Activation, Mesenchymal Stromal Cells}, issn = {1757-6512}, doi = {10.1186/scrt392}, author = {Valencic, Erica and Loganes, Claudia and Cesana, Stefania and Piscianz, Elisa and Gaipa, Giuseppe and Biagi, Ettore and Tommasini, Alberto} } @article {1780, title = {Immunomodulatory drugs in autoimmune lymphoproliferative syndrome (ALPS).}, journal = {Pediatr Blood Cancer}, volume = {58}, year = {2012}, month = {2012 Feb}, pages = {310; author reply 311}, keywords = {Antineoplastic Agents, Autoimmune Lymphoproliferative Syndrome, Diseases in Twins, Humans, Male, Pentostatin}, issn = {1545-5017}, doi = {10.1002/pbc.23205}, author = {Tommasini, Alberto and Valencic, Erica and Piscianz, Elisa and Rabusin, Marco} } @article {1844, title = {Inflammation profile of four early onset Crohn patients.}, journal = {Gene}, volume = {493}, year = {2012}, month = {2012 Feb 10}, pages = {282-5}, abstract = {

Crohn disease (CD) is a multifactorial disorder affecting mainly young adults. Sometimes, however, it can present in the first year of life (Early onset Crohn disease (EOCD)) showing an unpredictable course and can often be more severe than at older ages. Some cases have been associated to an underlying primary immunodeficiency such as IL10R deficiency. We studied the functional response to IL-10 and the genotype of IL-10 receptor in four patients with early onset crohn-like colitis. We found an IL10R variant, which may be associated with a decreased response to the cytokine in one patient. Further studies to determine its pathogenic effect should be performed. In addition IL-10 mediated inhibition of LPS-induced TNFα expression was measured in patient{\textquoteright}s monocytes.

}, keywords = {Crohn Disease, Cytokines, Humans, Inflammation, Monocytes, Nod2 Signaling Adaptor Protein, Polymorphism, Genetic, Receptors, Interleukin-10, Tumor Necrosis Factor-alpha}, issn = {1879-0038}, doi = {10.1016/j.gene.2011.11.043}, author = {Marcuzzi, Annalisa and Girardelli, Martina and Bianco, Anna Monica and Martelossi, Stefano and Magnolato, Andrea and Tommasini, Alberto and Crovella, Sergio} }